Loss of Expression of Antiangiogenic Protein FKBPL in Endometrioid Endometrial Carcinoma: Implications for Clinical Practice

Background and Objectives: FK506 binding protein like (FKBPL) is a member of the immunophilin family, with anti-angiogenic effects capable of inhibiting the migration of endothelial cells and blood vessel formation. Its role as an inhibitor of tumor growth and angiogenesis has previously been shown in studies with breast and ovarian cancer. The role of FKBPL in angiogenesis, growth, and carcinogenesis of endometrioid endometrial carcinoma (EEC) is still largely unknown. The aim of this study was to examine the expression of FKBPL in EEC and benign endometrial hyperplasia (BEH) and its correlation with the expression of vascular endothelial factor-A (VEGF-A) and estrogen receptor alpha (ERα). Materials and Methods: Specimens from 89 patients with EEC and 40 patients with BEH, as well as histological, clinical, and demographic data, were obtained from the Clinical Hospital Centre Zemun, Belgrade, Serbia over a 10-year period (2010–2020). Immunohistochemical staining of the tissue was performed for FKBPL, VEGF-A, and ERα. Slides were analyzed blind by two pathologists, who measured the intensity of FKBPL and VEGF-A expression and used the Allred score to determine the level of ERα expression. Results: Immunohistochemical analysis showed moderate to high intensity of FKBPL expression in 97.5% (n = 39) of samples of BEH, and low or no expression in 93.3% (n = 83) of cases of EEC. FKBPL staining showed a high positive predictive value (98.8%) and a high negative predictive value for malignant diagnosis (86.7%). The difference in FKBPL expression between EEC and BEH was statistically significant (p < 0.001), showing a decrease in intensity and loss of expression in malignant tissues of the endometrium. FKBPL expression was positively correlated with ERα expression (intensity, percentage and high Allred score values) and negatively correlated with the expression of VEGF-A (p < 0.05 for all). Conclusions: FKBPL protein expression demonstrated a significant decrease in FKBPL in EEC in comparison to BEH tissue, with a high predictive value for malignancy. FKBPL might be emerging as a significant protein with antiangiogenic and antineoplastic effects, showing great promise for the diagnostic and therapeutic applications of its therapeutic derivatives in gynecological oncology

Prognostic value of survivin expression in Wilms tumor

Purpose: To determine survivin expression patterns in Wilms tumor (WT) and compare it with the expression in normal renal tissue. Also, to analyse cytoplasmic and nuclear survivin expression in relation to histological type, prognostic group and tumor stage. Methods: Immunohistochemical expression of survivin was analysed in 59 cases of primary WT and in 10 normal kidney specimens, taken from the same patients, but distant from the tumor. Results: 51 out of 59 cases of WT (86.44%) showed decreased cytoplasmic survivin expression and 4 out of 59 cases of WT (6.78%) showed nuclear overexpression of survivin. There was statistically significant difference in the frequency of decreased cytoplasmic expression of survivin in individual components of WT (p=0.005). Decreased cytoplasmic expression of survivin in epithelial, blastemal and stromal component was found significantly more often in low stage WT compared to high stage WT (Fisher exact test, p=0.0002, p=0.002, p=0.002, respectively). There was no statistically significant difference in the frequency of survivin nuclear overexpression between different stages of WT (Fisher exact test, p=0.564), histological types (Fisher exact test, p=0.915), or between different prognostic groups (Fisher exact test, p=1). Conclusion: Decreased survivin cytoplasmic expression or nuclear overexpression may be related to favorable prognosis of WT

Fractal analysis tools for early assessment of liver inflammation induced by chronic consumption of linseed, palm and sunflower oils

Objective: Inflammation is a biological response of tissue to harmful stimuli. A high-fat diet was linked to low-grade chronic liver inflammation, which can further lead to more severe health conditions. It is crucial to assess the intensity of inflammation and structural tissue changes to reduce the subjective judgment by the examiner. We propose fractal-based methods for early-stage low-degree liver inflammation grading. Methods: We have randomly divided 40 C57BL/6 female mice into four groups (control, linseed oil, palm oil, sunflower oil). After 100 days, animals were euthanized, and liver tissue collected for analyses. We performed calculations of fractal dimension, fractal lacunarity, multifractal spectra, local fractal dimension, and particle metrics, applicable to tissue segmentation and grading. Results: Pathohistological analysis of some liver tissue showed a low-grade inflammatory infiltrate around the portal vein of experimental groups subjected to different high-fat diets. Differences in fractal dimension and lacunarity of the inflamed tissue were, in most cases, statistically significant between the high-fat diet groups. Both the observed intensity and area of inflammation were lowest for the sunflower oil. The results of standard fractal analysis, local fractal analysis, and particle analysis were in an excellent agreement. Conclusions: This study demonstrated the efficiency of the fractal analysis based tools in the quantification of complexity and early-stage structural changes in inflamed liver tissue, which could potentially be used in the diagnostic workup of inflammation in the liver. The presented methods could be implemented within a wider scope computer-aided diagnostics system in a very straightforward manner

Homogeneous static magnetic field of different orientation induces biological changes in subacutely exposed mice

It has been shown that static magnetic field (SMF) of moderate intensity produces considerable impact on biological systems. SMF can be homogeneous or inhomogeneous. In many studies, inhomogeneous SMF was employed. Aware that inhomogeneous SMF could result in experimental variability, we investigated the influence of a vertical homogeneous SMF of different orientation. Male Swiss-Webster 9- to 10-week-old mice were subacutely exposed to upward- and downward-oriented SMF of 128 mT generated by a cyclotron for 1 h/day during a 5-day period. We found that SMF affected various organs and that these effects were, to some degree, dependent on SMF orientation. Both upward- and downward-oriented SMF caused a reduction in the amount of total white blood cells (WBC) and lymphocytes in serum, a decrease of granulocytes in the spleen, kidney inflammation, and an increase in the amount of high-density lipoprotein (HDL). In addition, upward-oriented SMF caused brain edema and increased spleen cellularity. In contrast, downward-oriented SMF induced liver inflammation and a decrease in the amount of serum granulocytes. These effects might represent a specific redistribution of pro-inflammatory cells in blood and among various organs. It appears that homogeneous SMF of 128 mT affected specific organs in the body, rather than simultaneously and equally influencing the entire body system